Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers
文献类型：期刊论文
| 作者 | Cheng, Jinming1,2; Wu, Leilei1,2; Li, Yixue1,2,5; Yang, Liguang2; Hou, Ting2; Ding, Guohui2; Li, Hong2; Wei, Dongkai3; Li, Guang3; Ji, Yuan4 |
| 刊名 | GENOME MEDICINE
 |
| 出版日期 | 2018 |
| 卷号 | 10期号:-页码:42 |
| 关键词 | Hepatocellular carcinoma Methylation CpG island methylator phenotype Gene regulation Specific diagnostic biomarker |
| ISSN号 | 1756-994X |
| DOI | 10.1186/s13073-018-0548-z |
| 文献子类 | Article |
| 英文摘要 | Background: Hepatocellular carcinoma (HCC) is the one of the most common cancers and lethal diseases in the world. DNA methylation alteration is frequently observed in HCC and may play important roles in carcinogenesis and diagnosis. Methods: Using the TCGA HCC dataset, we classified HCC patients into different methylation subtypes, identified differentially methylated and expressed genes, and analyzed cis-and trans-regulation of DNA methylation and gene expression. To find potential diagnostic biomarkers for HCC, we screened HCC-specific CpGs by comparing the methylation profiles of 375 samples from HCC patients, 50 normal liver samples, 184 normal blood samples, and 3780 samples from patients with other cancers. A logistic regression model was constructed to distinguish HCC patients from normal controls. Model performance was evaluated using three independent datasets (including 327 HCC samples and 122 normal samples) and ten newly collected biopsies. Results: We identified a group of patients with a CpG island methylator phenotype (CIMP) and found that the overall survival of CIMP patients was poorer than that of non-CIMP patients. Our analyses showed that the cis-regulation of DNA methylation and gene expression was dominated by the negative correlation, while the transregulation was more complex. More importantly, we identified six HCC-specific hypermethylated sites as potential diagnostic biomarkers. The combination of six sites achieved similar to 92% sensitivity in predicting HCC, similar to 98% specificity in excluding normal livers, and similar to 98% specificity in excluding other cancers. Compared with previously published methylation markers, our markers are the only ones that can distinguish HCC from other cancers. Conclusions: Overall, our study systematically describes the DNA methylation characteristics of HCC and provides promising biomarkers for the diagnosis of HCC. |
| 学科主题 | Genetics & Heredity |
| WOS关键词 | PROMOTER METHYLATION ; CANCER ; PROGNOSIS ; MARKERS |
| 语种 | 英语 |
| WOS记录号 | WOS:000433443500001 |
| 出版者 | BMC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1032]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Dept Bioinformat & Biostat, Shanghai, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai, Peoples R China; 3.Basepair Biotechnol Co Ltd, Suzhou, Peoples R China; 4.Fudan Univ, Zhongshan Hosp, Dept Pathol, Shanghai, Peoples R China; 5.Shanghai Acad Sci & Technol, Shanghai Ctr Bioinformat Technol, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Cheng, Jinming,Wu, Leilei,Li, Yixue,et al. Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers[J]. GENOME MEDICINE,2018,10(-):42. |
| APA | Cheng, Jinming.,Wu, Leilei.,Li, Yixue.,Yang, Liguang.,Hou, Ting.,...&,.(2018).Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers.GENOME MEDICINE,10(-),42. |
| MLA | Cheng, Jinming,et al."Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers".GENOME MEDICINE 10.-(2018):42. |
入库方式： OAI收割
来源：上海营养与健康研究所
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